Anomalous functioning of the prefrontal regions have been hypothesized to impair an individual's ability to monitor and inhibit behavior, and therefore may lead to greater risk for initiation of substance use as well as hinder the discontinuation of substance use. Evidence for frontal/executive impairments in individuals who are substance abusers has been documented in neurocognitive investigations, as well as structural and functional neuroimaging studies, offering evidence for deficits in this system. The anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) share strong reciprocal connections, and have been shown to be part of the neural network underlying executive functioning. Recent neuroimaging findings indicate specific roles for subdivisions of the ACC and DLPFC in normal controls during a task of behavioral inhibition (Gruber et al., 2002). Based on these findings, we propose that cognitive control is comprised of two complementary interactive functions mediated by the ACC and the DLPFC. This project proposes the application of two complementary techniques to examine the integrity of the frontal lobes: functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to 12 normal control subjects, 12 chronic cocaine abusers and 12 heavy marijuana smokers. While BOLD fMRI techniques allow for the examination of cortical activity within discrete regions of interest, DTI provides a quantitative estimate of white matter integrity, crucial to the interpretation of functional changes within neural systems. To date, no study has incorporated focal fMRI BOLD techniques using cognitive challenge paradigms and DTI to examine the function and underlying structure of subdivisions of the ACC and DLPFC, two key components of the frontal executive system. Data generated from this investigation may provide new insights into the neural mechanisms of inhibitory processing, and decision-making, which has implications for substance abusing individuals. Additionally, findings from this project will provide the foundation for future grant applications aimed at examining the role of the prefrontal cortex in substance abuse.